a. Clinical Syndrome.
(a) The trichothecene mycotoxins are a diverse group of more than 40 compounds produced by fungi. They are potent inhibitors of protein synthesis, impair DNA synthesis, alter cell membrane structure and function, and inhibit mitochondrial respiration. Secondary metabolizes of fungi, such as T-2 toxin and others, produce toxic reactions called mycotoxicoses upon inhalation or consumption of contaminated food products by humans or animals. Naturally occurring trichothecenes have been identified in agricultural products and have been implicated in a disease of animals known as moldy corn toxicosis or poisoning.
(b) There are no well-documented cases of clinical exposure of humans to trichothecenes. However, strong circumstantial evidence has associated these toxins with alimentary toxic aleukia (ATA), the fatal epidemic seen in Russia during World War II, and with alleged BW incidents (“yellow rain”) in Cambodia, Laos and Afghanistan.
(2) Clinical Features.
(a) Consumption of these mycotoxins results in weight loss, vomiting, skin inflammation, bloody diarrhea, diffuse hemorrhage, and possibly death. Clinical signs in experimental animals (calves) given 0.08-0.64 mg T-2/kg/day for nine days included loss of appetite, weight loss, an increase in prothrombin time, and an increased serum aspartate amino transferase level. The onset of illness following acute exposure to T-2 (IV or inhalation) occurs in hours, resulting in the rapid onset of circulatory shock characterized by reduced cardiac output, arterial hypotension, lactic acidosis and death within 12 hours.
(b) Clinical signs and symptoms of ATA were hemorrhage, leukopenia, ulcerative pharyngitis, and depletion of bone marrow. The purported use of T-2 as a BW agent resulted in an acute exposure via inhalation and/or dermal routes, as well as oral exposure upon consumption of contaminated food products and water. Alleged victims reported painful skin lesions, lightheadedness, dyspnea, and a rapid onset of hemomhage, incapacitation and death. Survivors developed a radiation-like sickness including fever, nausea, vomiting, diarrhea, leukopenia, bleeding, and sepsis.
(1) Routine Laboratory Findings. Hematological alterations in the rodent model (parenteral routes) include marked but transient leukocytosis, characterized by rapid lymphocytosis and a mild neutrophilia. This is followed by a leukopenia that returns to normal values 4-7 days post-exposure. There is a reduced hematocrit with the presence of nucleated erythrocytes. Serum proteins and enzymes are not significantly altered after this acute exposure.
(2) Differential Diagnosis. Other diagnoses to consider include radiation toxicity and plant or chemical toxicity.
(3) Specific Laboratory Diagnosis. Specific diagnostic modalities are limited to reference laboratories. Gas-liquid chromatography (GC) and high pressure liquid chromatography (HPLC) have been used for detecting T-2 and related trichothecene mycotoxins in plasma and urine. Polyclonal and monoclinal antibodies to trichothecenes are also available for detection in liquid or solid samples after solvent extraction. Because of their long “half-life” the toxin metabolizes can be detected as late as 28 days after exposure. Between 50-75% of the parent toxin and metabolizes are eliminated in urine and feces within 24 hours. Urine should be the biological fluid chosen for diagnostic purposes. A one time urine sample with 0.10cc concentrated hydrochloric acid (HCI) added per 100cc of urine, to kill unwanted bacteria, should be submitted for analysis if the exposure was a recent one. Trichothecene mycotoxins can be detected in the urine out to approximately 14 days after exposure but if several days have elapsed since exposure, a 24 hour urine collection with HCI added should be submitted instead of a one time collection. The urine does not need to be kept refrigerated.
c. Therapy. General supportive measures are used to alleviate acute T-2 toxicoses. Prompt (within 5-60 min of exposure) soap and water wash significantly reduces the development of the localized destructive, cutaneous effects of the toxin. After oral exposure management should include standard therapy for poison ingestion. Of note is a superactivated charcoal (such as Superchartm, Gulf Bio Systems, Inc., Dallas, TX). Superchartm oral may offer an advantage over regular activated charcoal in that one needs to see approximately five times the dose of activated charcoal to gain an equivalent outcome to that if Superchartm is used. Superactivated charcoal is becoming standard in emergency management of poison ingestion. This substance has an extremely large surface area, two to three times that of regular activated charcoal. Superchar™ oral treatment (1-7 g/kg, po) either immediately or 1 to 3 hours after toxin exposure significantly increases survival times of animals. Some benefit may be derived from giving activated charcoal as late as 5 hours after exposure to T-2 toxins. In animal studies, dexamethasone (1-10 mg/kg, IV) administered as late as 3 hours after exposure to T-2 toxin improved survival and reduced the incidence of massive bloody diarrhea. No antitoxin is presently available for human use.
d. Prophylaxis. Ascorbic acid (400-1200 mg/kg, inter-peritoneal (ip)) works to decrease lethality in animal studies, but has not been tested in humans. While not yet available for humans, administration of large doses of monoclinal antibodies directed against T-2 and metabolizes have shown prophylactic and therapeutic efficacy in animal models.